first-trimester neutrophil-to- lymphocyte and …
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Al-Azhar Med. J. ( Surgery ). Vol. 50(2), April, 2021, 1059 - 1074
DOI: 10.12816/amj.2021.158456
https://amj.journals.ekb.eg/article_158456.html
1059
FIRST-TRIMESTER NEUTROPHIL-TO-
LYMPHOCYTE AND PLATELET-TO-
LYMPHOCYTE RATIOS AS INDICATORS FOR
EARLY DIAGNOSIS OF PREECLAMPSIA
By
Ahmed Gamal El-Din Mahmoud, Mohamed Ali Mohamed, El-Sayed
Ahmed El-Desouky and Mohamed Saad El-Din Radwan*
Departments of Obstetrics & Gynecology and Clinical Pathology*, Faculty of Medicine,
Al-Azhar University, Egypt
Corresponding author: Ahmed Gamal El-Din Mahmoud: Obstetrics & Gynecology
resident at Helwan General Hospital, Egypt, Mobile: +201010478681
ABSTRACT
Background: Preeclampsia is a popular obstetric complication. Neutrophil to lymphocyte ratio (NLR) and
platelet-to-lymphocyte ratio (PLR) have gained notable attention as systemic inflammatory response
indicators in diverse clinical settings.
Objective: To evaluate the diagnostic worth NLR and PLR during the first trimester of gestation to forecast
the subsequent occurrence of preeclampsia.
Patients and methods: The present study was a prospective cohort study that enrolled 300 pregnant ladies.
Initial CBC was done for all eligible cases at 7-14 weeks of gestation then cases were followed up till
delivery.
Results: The results showed progressively statistically increase in the mean NLR in PE cases compared to
control cases and a statistically significant difference between the control and PE cases s regard PLR. Cut off
value 1.7538 NLR can differentiate normotensive pregnant women from preeclampsia women with
sensitivity of 86.5 %, specificity of 91.6% %, PPV of 64 %, and NPV of 97.5 %. However, PLR can
differentiate normotensive pregnant women from preeclampsia women at a cut off value 80.70 with
sensitivity of 81.1 %, specificity of 95.1 %, PPV of 28.6 %, and NPV of 64.6 %.
Conclusion: Neutrophil to lymphocyte ratio and platelet to lymphocyte ratios is cheap, simple, rapid, and
readily accessible marker that may be beneficial to predict preeclampsia in early pregnancy. Hence, these
easy applicable parameters can be applied as low-cost predictive factors for the development of PE.
Keywords: Preeclampsia, Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte Ratio (PLR).
INTRODUCTION
The search for novel predictive
markers residues as an unaccomplished
goal since the pathogenesis of
preeclampsia has not been entirely
explicated (Melchiorre et al., 2014).
The clinical consumption of
biomarkers for risk prediction, pre-clinical
diagnosis, and to define cases more
predisposed to develop complications is
broadly reviewed to a better
understanding of the preeclampsia
pathophysiology (de Siqueira et al.,
2017).
Normal pregnancies are associated
with a degree of systemic inflammation.
AHMED GAMAL EL-DIN MAHMOUD et al., 1060
Furthermore, PE is correlated with a
maladaptive immune response of T-helper
(TH) 1 cells and TH 2 cells and hyper-
inflammatory state (Kim et al., 2018).
In the last preceding years, elevated
neutrophil-to-lymphocyte ratio (NLR) and
platelet-to-lymphocyte ratio (PLR) have
gained noteworthy attention as systemic
inflammatory response markers in a
multitude of clinical conditions (Qin et al.,
2016).
Based on the pathogenesis of PE, this
study was designed to evaluate the
diagnostic efficiency of NLR and PLR, as
well as neutrophil, lymphocyte and
platelet counts through the first trimester
of gestation to expect the consequent
occurrence of preeclampsia.
PATIENTS AND METHODS
The present study enrolled 300
pregnant females who attended the
departments of Obstetrics and Gynecology
at Helwan General and Al-Azhar
University during the period of research
from December 2017 to December 2019.
Inclusion criteria:
Pregnant women from 7-14 weeks,
primigravida or multigravida with or
without history of preeclampsia.
Exclusion criteria:
Systemic diseases, history of
hematopoietic system disorders,
malignancies, acute or chronic
inflammatory diseases, or on any
medication which could have affected the
CBC results.
The selected patients were subjected to
thorough history taking complete general
and abdominal examination, examination
by abdominal ultrasound.
Blood samples were drawn in the first
trimester; a 5 ml of the blood was
collected on EDTA tube for routine CBC
by Sysmex the automated hematology
analyzer SF-300, Japan. The NLR and the
PLR ratios were calculated as the ratio of
neutrophil count to lymphocyte count and
the ratio of platelet count to lymphocyte
count respectively.
Cases were followed up on routine
antenatal care visits and were included
into four groups: 215 preeclampsia free
pregnant women (control) after the 20th
week of gestation, 37 pregnant women
who developed preeclampsia diagnosed
according to the American College of
Obstetrics and Gynecology (ACOG)
(2013), 22 pregnant Egyptian women who
failed to complete their pregnancy (had
abortion), and 26 study participants who
were excluded from the present study due
to loss of follow-up.
Approval of ethical committee was
obtained from quality education assurance
unit, Al-Azhar university faculty of
medicine, Egypt. An informed consent
was taken from every woman before
participation in this study. The nature and
aim of this work were fully discussed to
all women who agreed to participate in the
study. Patients were explained the
procedure.
Statistical analysis:
All statistical calculations were done
using computer programs SPSS
(Statistical Package for the Social
Science; SPSS Inc., Chicago, IL, USA)
version 23 for Microsoft Windows Data
were statistically described in terms of
FIRST-TRIMESTER NEUTROPHIL-TO-LYMPHOCYTE AND… 1061
mean ± standard deviation (SD), or
median and range. Categorical data were
summarized as percentages. Comparison
of numerical variables between the study
groups was done using Mann-whitney U
test, and one way ANOVA test followed
by post-hoe test. For comparing
categorical data, Chi square (χ2) test was
performed. Receiver operator
characteristic (ROC) analysis was used to
determine the optimum cut off value for
the studied diagnostic markers.
Correlations between different parameters
were done using spearman’s and Pearson's
correlation coefficient and the area under
the curve (AUC). The probability (P)
values of ≤0.05 were considered
statistically significant.
Sample size justification: MedCalc®
version 12.3.0.0 program was used for
calculations of sample size; statistical
calculator based on 95% confidence
interval and power of the study 80% with
α error 5%.
RESULTS
The mean age in the present study was
30.14 ± 5.22 years in control group, 29.35
± 6.95 years in preeclampsia group, and
26.73 ± 4.72 in miscarriage group (P=
0.019).
There were no statistically significant
differences between the mean age of cases
in preeclampsia group and control
subjects (P >0.05). Also, there was no
statistically significant difference between
all studied groups according to gravidity,
parity, and body mass index.
In preeclampsia cases, the mean
gestational age at delivery was 34.66±3.53
weeks while it was 37.33±2.04 weeks in
control cases.
These results revealed that there was
significant decrease in the mean
gestational age at delivery in preeclampsia
group control group (P <0.001).
As regard number of fetuses, it was
found that multiple gestation was found in
10 (4.6%), and 8 (21.6%) of control and
preeclampsia groups respectively, with a
statistically significant difference between
groups (P-value=0.002).
Considering neonatal birth weight after
delivery, 7 (18.9%) of newborns to
preeclampsia mothers had weight less
than 1000g: 4(10.8%) of them had weight
ranged from 1000-1499 g. In another
23(62.2%) cases, weight at birth was
1500-2499 g. It was only in 3 (8.1%)
cases weight at the time of birth was
recorded to be >2500g. Mean of weight at
birth was 1686.75±683.01g ranged from
750 - 4000 g in preeclampsia group
compared to 3310.5 ± 340.85 grams in the
controls (P <0.001).
Complications were observed in
mothers who suffered from preeclampsia
as follow: only 1 case (2.7%) had HELLP,
and 3(8.1%) had eclampsia, whereas there
were 8 cases (3.7%) in control group had
PPROM.
There was a significant difference
between the studied groups with regards
to blood pressure both systolic and
diastolic which increased with the
occurrence of preeclampsia (P<0.001).
The study showed that the average
systolic blood pressure among cases was
found to be 160.54 ± 20.13 mmHg
compared with 113.58 ± 9.79 mmHg
among controls. Average diastolic blood
pressure was found to be 103.95 ± 11.55
mmHg among preeclampsia cases
AHMED GAMAL EL-DIN MAHMOUD et al., 1062
compared with 71.07 ± 6.21 mmHg
among controls.
All control cases have no proteinuria
whereas, in preeclampsia group, fourteen
(37.8%) of the cases showed proteinuria
level ranged from (+ - ++), whereas 23
(62.2%) of them showed a level ranged
from (+++ - ++++). There was a
significant difference between the studied
groups with regards to appearance of
protein in urea which increased in patients
with preeclampsia (P<0.001).
The results showed that the mean ± SD
of hematological parameters was 12.86 ±
1.23 Vs 12.18 ± 1.08 g/dL for the
hemoglobin, 4.1 ± 0.312 Vs 3.99 ± 0.062
(106/µL) for the red blood cell count
(RBCs). Also, the mean platelets count
was 268.273 ± 45.850 Vs 222.127 ±
73.398 (103/µL), and the mean white
blood cells count (WBCs) was 7.969 ±
3.009 Vs 11.467 ± 2.352 in control, and
preeclampsia groups respectively.
These results revealed that there was
significantly decrease in the mean value of
platelets counts and hemoglobin levels in
preeclampsia cases when compared to
healthy control (P<0.001 & P = 0.002;
respectively). There was a significant
increase in WBCs in preeclampsia
patients when compared to control group
(P < 0.001). No significant difference we
found in the mean value of RBCs between
studied groups (P > 0.05).
Mean neutrophils was higher in women
with pre-eclampsia compared with women
in the control group (7043.59± 1494.7 vs
4265.1± 1627.33/ µL; P<0.001). Values
were also significantly higher in patents
with pre-eclampsia compared with healthy
pregnant controls for lymphocysts
(3404.49± 823.84 vs 2944.47 ± 1113.45/
µL; P=0.004).
Regarding neutrophil to lmphocye ratio
(NLR), the results showed a progressively
increase in the mean NLR in PE cases
compared to control cases (2.11 ± .0.36)
and (1.46 ± 0.19) respectively. There was
a statistically significant difference
between patients with PE and healthy
pregnant women (P<0.001) (Figure 1).
Figure (1): Mean of NLR among patients and control groups.
FIRST-TRIMESTER NEUTROPHIL-TO-LYMPHOCYTE AND… 1063
Also, platelets to lymphocyte ratio
(PLR) showed a statistically significant
difference between the control and PE
cases (P<0.001), as the mean PLR in
control cases was (103.3 ± 39.3)
compared to (70.38 ± 37.2) in
Preeclampsia cases (Figure 2). Table 1
summarizes the demographic data and
biochemical parameters of the patients
and controls.
Figure (2): Mean of PLR among patients and control groups.
AHMED GAMAL EL-DIN MAHMOUD et al., 1064
Table (1): Demographic data and biochemical parameters of the patients and
controls
Groups
Variables
Healthy
Controls
(n=215)
Preeclampsia
Group
(n=37)
P-value
Mann
Whitney test
Age(Yrs.) 30.14 ± 5.22 29.35 ± 6.95 0.514
Gestational age at delivery
(weeks) 37.33±2.04 34.66±3.53 <0.001**
BMI at enrollment 27.03 ± 3.08 27.79 ± 6.75 0.503
Systolic Blood Pressure
(mmHg ) 113.58 ± 9.79
160.54 ±
20.13 <0.001**
Diastolic Blood Pressure
(mmHg ) 71.07 ± 6.21
103.95 ±
11.55 <0.001**
Gravidity 2.81 ± 1.58 2.76 ± 1.66 0.840
Parity 0.312 ± 0.46 0.324 ± 0.63 0.885
Number of fetuses.
Singleton
Multiple
205(95.3%)
10(4.7%)
29(78.4%)
8(21.6%)
0.002**
Appearance of proteinuria
None
1-2
3-4
215(100%)
0(0%)
0(0%)
0(0%)
14(37.8%)
23(62.2%)
0.001**
Birth weight [g] 3310.5 ± 340.85 1686.75 ±
683.01 <0.001**
Complications
None
PPROM
HELLP
Eclampsia
207(96.3%)
8(3.7%)
0(0%)
0(0%)
33(89.2%)
0(0%)
1(2.7%)
3(8.1%)
<0.001**
Hemoglobin (g/dL) 12.86 ±1.23 12.18 ± 1.08 0.002**
RBCs count (×106/ μL) 4.1 ± 0.312 3.99 ± 0.62 0.318
Leukocytes count (x103/
μL) 7.969 ± 3.009
11.467 ±
2.352 <0.001**
Neutrophils (/μl) 4265.1±
1627.33
7043.59±
1494.7 <0.001**
Lymphocytes (/μl) 2944.47 ±
1113.45
3404.49±
823.84 0.004**
PLT (×103/ μL) 268.273 ±
45.850
222.127 ±
73.398 <0.001**
NRL 1.46 ± 0.19 2.11 ± .0.36 <0.001**
PLR 103.3 ± 39.3 70.38 ± 37.2 <0.001**
Values are expressed as mean ± standard deviation or n (%) unless otherwise specified;
BMI — body mass index; NLR — neutrophil to lymphocyte ratio; PLR — platelet to lymphocyte ratio
The mean NLR had significant positive
correlation with systolic and diastolic
blood pressure, and WBCs (p<0.05). Also,
it had significant negative correlation with
gestational age, birth weight, and PLTs
(p<0.05). In addition, PLR was
significantly positive correlated with
gestational age, birth weight, proteinuria,
hemoglobin, and PLTs, whereas it was
negatively correlated with BMI, systolic
and diastolic blood pressure, albumin and
WBCs (p<0.05) (Table 2).
FIRST-TRIMESTER NEUTROPHIL-TO-LYMPHOCYTE AND… 1065
Table (2): Correlation between NLR and PLR and other studied parameters
Groups
Parameters
NLR PLR
r P-value r P-value
NLR 1.000 - -0.123 0.053
PLR -0.123 0.053 1.000 -
Age )years) -0.041 0.514 0.058 0.343
Gestational age (weeks) -0.196 0.002** 0.390 <0.001**
Birth weight (g) -0.526 <0.001** 0.322 <0.001**
Gravidity 0.084 0.185 0.009 0.884
Parity 0.045 0.480 0.038 0.531
BMI (Kg/m2) 0.091 0.150 -0.147 0.016*
Systolic Blood pressure (mmHg) 0.597 <0.001** -0.276 <0.001**
Diastolic Blood Pressure (mmHg) 0.656 <0.001** -0.297 <0.001**
Proteinuria 0.092 0.590 0.297 <0.025*
Hemoglobin (g/dL) -0.047 0.460 0.190 0.003*
WBCs (×103/ μL) 0.292 <0.001** -0.796 <0.001**
Platelet count (×103/ μL) -0.275 <0.001** 0.453 <0.001**
RBCs (×106/ μL) 0.008 0.905 -0.071 0.247
In this study, the optimal cut-off levels
of NLR and PLR parameters for
prediction of development of
preeclampsia were identified using ROC
analysis. ROC curve analysis showed that
NLR can differentiate normotensive
pregnant women from preeclamptic
pregnant women at a cut off value 1.7538
with sensitivity of 86.5 % and specificity
of 91.6% %, PPV of 64 %, NPV of 97.5
% and AUROC was 0.961(P<0.001).
However, PLR can differentiate
normotensive pregnant women from
preeclamptic pregnant women at a cut off
value 80.70 with sensitivity of 81.1 % and
specificity of 95.1 %, PPV of 28.6 %,
NPV of 64.6 %. The area under the curve
(AUC= was 0.768; CI :( 0.691-0.846)),
the previous results indicating the two
parameters are important for predicting
preeclampsia (Figures 3-4).
Figure (3): ROC curve of NLR for discriminating preeclampsia patients from
healthy volunteers
AHMED GAMAL EL-DIN MAHMOUD et al., 1066
Figure (4): ROC curve of PLR for discriminating preeclampsia patients from
healthy volunteers.
DISCUSSION
Platelets, neutrophils, and lymphocytes
are major blood parameters allied to
immune surveillance, and the
platelet/lymphocyte ratio (PLR) and the
netrophils/lymphocyte ratio (NLR) play
an important role in cytokine-dependent
immune response. It was proposed that
PLR was a more sensitive marker of
systemic inflammation in various
conditions. Although association of PLR
with inflammation and numerous diseases
was reported, there are limited data
evaluating the association of PLR and PE
(Kholief et al., 2019).
As regard results of initial
hematological parameters recorded at the
beginning of the study, these results
revealed that there was a significantly
decrease in the mean value of platelets
counts in preeclampsia cases when
compared to healthy control. These
findings were in agreement with other
studies that found significant decrease in
platelet count (Alkholy et al., 2013 and
Vilchez et al., 2017).
Fluid retention occurs during
pregnancy because of sodium and water
retention owing to estrogen and
progesterone hormone effects, leading to
hemodilution or pseudo-
thrombocytopenia. The underlying trigger
of thrombocytopenia in hypertensive
pregnant woman is mysterious. It was
proposed that, to an increased vascular
tone during pregnancy, inducing platelet
destruction and coagulation defects also
ensue. Moreover, increased platelet-
related IgG serum level may occur in
some hypertensive pregnant women. Yet,
the increase in immunoglobulin is non-
specific and does not inevitably indicate
an immunologic-mediated
thrombocytopenia (Habas et al., 2013).
Moreover, contact of platelets with the
damaged endothelium stimulates the
coagulation cascade, which can increase
FIRST-TRIMESTER NEUTROPHIL-TO-LYMPHOCYTE AND… 1067
both consumption and bone marrow
production of platelets (AlSheeha et al.,
2016).
In addition, there was a statistically
significant decrease in the mean value of
hemoglobin (Hb) levels in preeclampsia
cases when compared to their healthy
counterparts. There was no significant
difference in the mean value of RBCs
between studied groups. These results
were in line with the findings reported by
Khoigani et al. (2012) who conducted a
study in the first and second half of the
pregnancy separately. They concluded
that Low Hb values during the first
pregnancy half was related to
preeclampsia occurrence.
Prior literature have also reported low
maternal Hb levels in preeclampsia and
this was thought to be a reflection of low
socio-economic and poor nutritional state
in developing nations (Cordina et al.,
2015).
Monteiro et al. (2014) showed that the
Hb concentration did not vary
significantly between normotensive and
females with preeclampsia. In discordance
to the present work, Hassan and his Co-
workers (2016) showed that there was an
increase in maternal Hb levels but without
any statistical significance. Also, Nasiri et
al. (2015) and Ali (2016) showed that the
women with preeclampsia had a higher
mean of hemoglobin.
At this point, there is a controversial
question in which trimesters the
hemoglobin can better forecast
preeclampsia. Nasiri et al. (2015) stated
that the second trimester was more
informative than other trimesters. Results
of the current study revealed a significant
increase in WBCs in preeclampsia
patients when compared to control group.
Moreover, mean neutrophils were higher
in women with pre-eclampsia compared
with women in the control group. Values
were also signifcantly higher in patents
with pre-eclampsia compared with healthy
pregnant controls for lymphocysts.
Canzoneri et al. (2010) have showed
that increased total leukocyte count was
related to both preeclampsia and disease
severity. Neutrophilia was the only WBC
subgroup associated with severe
preeclampsia. Moreover, first trimester
leukocytosis is allied to unpleasant
pregnancy outcomes, particularly with
preterm delivery (Tzur et al., 2013). Gezer
et al. (2016) detected that the mean
neutrophil count in the first trimester was
significantly higher in patients who
developed preeclampsia. Alkredes and
Zaherra (2018) and Phaloprakarn et al.
(2018) showed a high WBC count among
women with preeclampsia as compared to
their control counterparts. Leukocytosis is
a physiologic change detected in healthy
pregnancies resultant from neutrophilia,
and WBCs are well-known to be the
mediator of inflammation (Örgül et al.,
2019). Örgül et al. (2019) found that
lymphocytes did not differ in preeclamptic
women compared with controls.
Regarding neutrophil to lymphocyte
ratio (NLR), the results showed
progressively increase in the mean NLR in
PE cases compared to control cases.
Yıldız et al. (2016) and Phaloprakarn
et al. (2018) found that NLR values were
greater in patients who established
preeclampsia. Neutrophils are reported to
have a role in in the inflammatory
processes. They are the first blood cells
AHMED GAMAL EL-DIN MAHMOUD et al., 1068
reacting to inflammation (Gezer et al.,
2016).
Nevertheless, Kurt et al. (2015)
reported higher neutrophil counts in
preeclamptic patients, inferring the
presence of an increased inflammatory
state, but they reported that NLR was not
significantly dissimilar between
preeclampsia and control groups.
Moreover, Yücel and Ustun (2017),
Kholief et al. (2019) and Örgül et al.
(2019) found decreased NLR from PE to
controls but without statistical
significance and they justified these
results by the small number of
participants.
Though NLR is easy to measure, its
utility as a marker of systemic
inflammation may be influenced by
numerous conditions such as maternal
systemic infections, maternal
malignancies, and chronic inflammatory
diseases (Yıldız et al., 2019). Thus, those
conditions were excluded from our work.
Considering platelets to lymphocyte
ratio (PLR), results of the present work
showed a statistically significant
difference between the control and PE
cases.
Generally, the results concerning to
PLR changes in preeclampsia are
conflicting, with both increased (Gezer et
al., 2016) and decreased levels (Yücel and
Ustun, 2017 and Mannaerts et al., 2019)
reported in the literature.
Platelets consumption after endothelial
injury brings about thrombocytopenia in
preeclampsia. As a result, researchers
have claimed that PLR levels may
decrease in preeclampsia which
Corresponds to our findings (Örgül et al.,
2019). Toptas and Colleagues (2016) also
found that PLR levels were comparable
between PE and normal pregnancies and
severe PE patients had lower PLR levels
compared with women with mild PE.
Studies that reported higher PLR in PE
than controls recommended that PLR was
a more sensitive marker of systemic
inflammation (Kholief et al., 2019).
In this study, ROC curve analysis
showed that NLR can differentiate
normotensive pregnant women from
preeclamptic pregnant women at a cut off
value 1.7538 with sensitivity of 86.5 %
and specificity of 91.6% %, PPV of 64 %,
NPV of 97.5 % and AUROC was 0.961.
This was lower than the cut of value
reported by Gezer et al. (2016) that was
3.08, with the sensitivity and specificity of
74.6% and70.1% respectively. The
receiver operating curve by Sachan et al.
(2017) showed significant diagnostic
accuracy of NLR between controls and PE
cases.
However, PLR can differentiate
normotensive pregnant women from
preeclamptic pregnant women at a cut off
value 80.70 with sensitivity of 81.1 % and
specificity of 95.1 %, PPV of 28.6 %,
NPV of 64.6 %. The cut of value reported
by Gezer et al. (2016) was 126.8 or
higher, with the sensitivity and specificity
of 71.8% and72.4% respectively to predict
preeclampsia. Kholief and his co-workers
(2017) reported a cut off value less than or
equal to 77.5 for PLR with 35.71%
sensitivity, 85.71% specificity, 83.3%
PPV, and 40% NPV. Yucel and Ustun
(2017) reported that the AUC for NLR,
PLR were not statistically significant
(p=0.636, and 0.104, respectively).
FIRST-TRIMESTER NEUTROPHIL-TO-LYMPHOCYTE AND… 1069
CONCLUSION
Multiple restraints of alpha fetoprotein
(AFP) highlighted the necessity and
urgency of identifying extra biomarkers
with the potential of being utilized per se
or complementing AFP for hepatocellular
carcinoma (HCC) diagnosis and
prognosis. Chromogranin A (CgA) may
act as such useful diagnostic as well as
prognostic biomarker for HCC as it was
significantly higher in patients with HCC
than in cirrhotic patients and it had higher
sensitivity, specificity than AFP for HCC
diagnosis. So, CgA is a good biomarker
for HCC detection.
Conflict of interest: The authors declare
that they have no conflicts of interest.
REFERENCES
1. Ali E (2016): Early Pregnancy
Hemoglobin Levels as Prediction of
Preeclampsia. International Journal of
Advanced Research, 4(10):16-19.
2. Alkholy EA, Farag EA, Behery MA and
Ibrahim MM (2013): The Significance of
Platelet Count, Mean Platelet Volume And
Platelet Width Distribution In
preeclampsia. Al-Azhar Assiut Medical
Journal, 11(1):200-214.
3. Alkredes A and Zaherra S (2018): The
Significance of Blood Parameters in
Womenwith Preeclampsia. International
Journal of Scientific & Engineering
Research, 9(1):714-718.
4. AlSheeha MA, Alaboudi RS, Alghasham
MA, Iqbal J and Adam I (2016): Platelet
count and platelet indices in women with
preeclampsia. Vascular Health and Risk
Management, 12:477-480.
5. American College of Obstetricians and
Gynecologists (2013): Hypertension in
pregnancy. Report of the American
College of Obstetricians and
Gynecologists’ task force on hypertension
in pregnancy. Obstetrics and Gynecology,
122(5):1122-13.
6. Canzoneri BJ, Lewis DF, Groome L and
Wang Y (2010): Increased neutrophil
numbers account for leukocytosis in
women with preeclampsia. American
Journal of Perinatology, 26:729–732.
7. Cordina M, Bhatti S, Fernandez M,
Syngelaki A, Nicolaides KH and
Kametas NA (2015): Maternal
hemoglobin at 27–29 weeks’ gestation and
severity of pre-eclampsia. The Journal of
Maternal-Fetal & Neonatal Medicine,
28(13):1575-1580.
8. de Siqueira Guida JP, Surita FG,
Parpinelli MA and Costa ML (2017):
Preterm Preeclampsia and Timing of
Delivery: A Systematic Literature Review.
Revista Brasileira de Ginecologia e
Obstetrícia/RBGO Gynecology and
Obstetrics, 39(11):622-631.
9. Gezer C, Ekin A, Ertas IE, Ozeren M,
Solmaz U, Mat E and Taner CE (2016):
High first-trimester neutrophil-to-
lymphocyte and platelet-to-lymphocyte
ratios are indicators for early diagnosis of
preeclampsia. Ginekologia Polska,
87(6):431-435.
10. Habas E, Rayani A and Ganterie R
(2013): Thrombocytopenia in hypertensive
disease of pregnancy. The Journal of
Obstetrics and Gynecology of India,
63(2):96-100.
11. Hassan B, Almushait M, Mubashar H
and Zia S (2016): The Role of Risk
Assessment at Antenatal Care Clinics in
the Prediction of Pre-Eclampsia in a High
Altitude Area. International Journal of
Clinical Medicine, 7(1):10-15.
12. Khoigani MG, Goli S and Hasan Zadeh
A (2012): The relationship of hemoglobin
and hematocrit in the first and second half
of pregnancy with pregnancy outcome.
AHMED GAMAL EL-DIN MAHMOUD et al., 1070
Iranian Journal of Nursing and Midwifery
Research, 2(l1):165-170.
13. Kholief A, Swilam R, Elhabashy A and
Elsherief R (2019): Neutrophil/
lymphocyte ratio, platelet/lymphocyte
ratio, and c-reactive protein as markers for
severity of pre-eclampsia. Research and
Opinion in Anesthesia and Intensive Care,
6(1):1-8.
14. Kim MA, Han GH, Kwon JY and Kim
YH (2018): Clinical significance of
platelet-to-lymphocyte ratio in women
with preeclampsia. American Journal of
Reproductive Immunology, 80(1):1-6.
15. Kirbas A, Ersoy AO, Daglar K, Dikici T,
Biberoglu EH, Kirbas O and Danisman
N (2015): Prediction of preeclampsia by
first trimester combined test and simple
complete blood count parameters. Journal
of Clinical and Diagnostic Research,
9(11):C20–C23.
16. Kurt RK, Aras Z, Silfeler DB, Kunt C,
Islimye M and Kosar O (2015):
Relationship of red cell distribution width
with the presence and severity of
preeclampsia. Clinical and Applied
Thrombosis/Hemostasis, 21(2):128-131.
17. Kurtoglu E, Kokcu A, Celik H, Tosun M
and Malatyalioglu E (2015): May ratio of
neutrophil to lymphocyte be useful in
predicting the risk of developing
preeclampsia? A pilot study. The Journal
of Maternal-Fetal & Neonatal Medicine,
28(1):97-99.
18. Mannaerts D, Heyvaert S, De Cordt C,
Macken C, Loos C and Jacquemyn Y
(2019): Are neutrophil/lymphocyte ratio
(NLR), platelet/lymphocyte ratio (PLR),
and/or mean platelet volume (MPV)
clinically useful as predictive parameters
for preeclampsia?. The Journal of
Maternal-Fetal & Neonatal Medicine,
32(9):1412-1419.
19. Melchiorre K, Sharma R and
Thilaganathan B. (2014): Cardiovascular
implications in preeclampsia: an overview.
Circulation, 130(8):703-714.
20. Monteiro G, Subbalakshmi NK and Pai
SR (2014): Relevance of measurement of
hematological parameters in subjects with
pregnancy induced hypertension. Nitte
University Journal of Health Science,
4(1):15-20.
21. Nasiri M, Faghihzadeh S, Majd HA,
Zayeri F, Kariman N and Ardebili NS
(2015): Longitudinal discriminant analysis
of hemoglobin level for predicting
preeclampsia. Iranian Red Crescent
Medical Journal, 17(3):1-7.
22. Örgül G, Haklı DA, Özten G, Fadiloğlu
E, Tanacan A and Beksaç MS (2019):
First trimester complete blood cell indices
in early and late onset preeclampsia.
Turkish Journal of Obstetrics and
Gynecology, 16(2):112-117.
23. Oylumlu M, Ozler A, Yildiz A, Oylumlu
M, Acet H, Polat N, Soydinc HE, Yuksel
M and Ertas F (2014): New inflammatory
markers in pre-eclampsia:
echocardiographic epicardial fat thickness
and neutrophil to lymphocyte ratio.
Clinical and Experimental Hypertension,
36(7):503-507.
24. Phaloprakarn C, Tangjitgamol S and
Manusirivithaya S (2018): Total White
Blood Cell Count and Its Subtypes in Early
Pregnancy and Later Development of
Preeclampsia. Journal of the Medical
Association of Thailand, 101(8):1-10.
25. Qin B, Ma N, Tang Q, Wei T, Yang M,
Fu H, Hu Z, Liang Y, Yang Z and
Zhong R (2016): Neutrophil to
lymphocyte ratio (NLR) and platelet to
lymphocyte ratio (PLR) were useful
markers in assessment of inflammatory
response and disease activity in SLE
patients. Modern Rheumatology,
26(3):372-376.
FIRST-TRIMESTER NEUTROPHIL-TO-LYMPHOCYTE AND… 1071
26. Sachan R, Patel ML, Sachan P and
Shyam R (2017): Diagnostic accuracy of
neutrophil to lymphocyte ratio in
prediction of nonsevere preeclampsia and
severe preeclampsia. Journal of Current
Research in Scientific Medicine, 3(2):79-
83.
27. Toptas M, Asik H, Kalyoncuoglu M,
Can E and Can MM (2016): Are
neutrophil/ lymphocyte ratio and
platelet/lymphocyte ratio predictors for
severity of preeclampsia?. Journal of
Clinical Gynecology and Obstetrics,
5(1):27-31.
28. Tzur T, Weintraub AY, Sergienko R
and Sheiner E (2013): Can leukocyte
count during the first trimester of
pregnancy predict later gestational
complications?. Archives of Gynecology
and Obstetrics, 287(3):421-427.
29. Vilchez G, Lagos M, Kumar K and
Argoti P (2017): Is mean platelet volume
a better biomarker in pre-eclampsia?.
Journal of Obstetrics and Gynaecology
Research, 43(6):982-990.
30. Yıldız Ç, Karakuş S, Akkar ÖB, Topbaş
T, Çetin M, Yanık A and Çetin A
(2016): The significance of neutrophil-
lymphocyte ratio and mean corpuscular
volume in diagnosis of preeclampsia.
Gynecology Obstetrics & Reproductive
Medicine, 22(2):75-79.
31. Yücel B and Ustun B (2017): Neutrophil
to lymphocyte ratio, platelet to lymphocyte
ratio, mean platelet volume, red cell
distribution width and plateletcrit in
preeclampsia. Pregnancy Hypertension: An
International Journal of Women's
Cardiovascular Health, 7:29-32.
AHMED GAMAL EL-DIN MAHMOUD et al., 1072
النسب الأولى من العدلات إلى الخلايا اللمفاوية ونسبة الصفائح الدموية إلى الخلايا الليمفاوية كمؤشرات للتشخيص
المبكر لمقدمات الارتعاج أحمد جمال الدين محمود، محمد علي محمد، السيد أحمد الدسوقي، محمد سعد الدين
* رضوان
، مصر ينيكية*، كلية الطب، جامعة الأزهرقسمي أمراض النساء والتوليد والباثولوجيا الإكل
يعددددت اع ضددددلد ددددء احددددتل امرددددلا احتحدددد لحدددد دددد ل دددد تددددت خلفيةةةةة البحةةةة
ددددلن احرلدددد احاددددلوت ددددص احتحدددد ا دددد ط لدددد ل ددددص يدددد اع ضددددلد ددددء احددددتل
. ايعددددت دددص بعدددت الألدددد اد احعطددد يص ددددص احتحددد بللأ دددلا احدددت الددددال ولن اددد اح ددددان
لا احتحدددد ددددص اادددد اححتددددل ضلء اححدددد تددددت امرددددلا احتحدددد اع ضددددلد ددددء احددددتل امردددد
. ابدددلح م دددص تدددا اع ضدددلد حدددت ا ددد اع حددد ل تدددت لددد احدددت احاادددل ااححددد تدددت ددد ل ا
% 5 دددء احدددتل امردددلا احتحددد ددد ي ادددل ح احتدددتا ددد و ددد تامددد حددد اا بددد ص
.% أل او يتحا لت تا ص الألئل احح ح يح الإللب ر ل بعت 10احت
هددددا ع ادددد احش حدددد اححط لدددد حر ددددى ليددددل احر ح اا دددد احددددت الهةةةةد مةةةةن البحةةةة
اح ليددددل احل حضلايدددد ااحلددددضل ى احت ايدددد احددددت اح ليددددل احل حضلايدددد ادددد احالدددد الأان ددددص
.احتح تح ا اء حلحط ص احح ك لأع ضلد ء احتل ح احتح
اح ددد تاء احتاا ددد لحددد دددص 300 ددد الددد اا احتعالددد لدددت المريضةةةاط و ةةةرث البحةةة
احححدددد للاء لددددت حطددددضت لدددداا احعددددلل ا حطددددض لء لل عدددد الوهدددد ادددد احضحدددد ددددص
.2019ا حت لي ح 2017لي ح
ألدددد اد حت ددددلو احر ح اا دددد احددددت 14-7اتددددت دددد حدددد دددداع لل تل لدددد ددددص
.اح ليل احل حضلاي او احلضل ى احت اي احت اح ليل احل حضلاي
اتددددت دددد حلبعدددد احتددددللء حددددت احددددالل حححلبعدددد و دددد اححعدددد ي ححدددد ي اع ضددددلد
احعحددد اح حدددت ردددت دددي اددد ال ح دددلع يشددد احدددالل ا دددء احدددتل دددح احتحددد دددح ال
.ظ اع احح ي ا رت احالل
FIRST-TRIMESTER NEUTROPHIL-TO-LYMPHOCYTE AND… 1073
تلودددن هردددلة ويدددلل ت ددد ا لدددل ل حعلددد بر ددد ليدددل احر ح اا ددد حدددت نتةةةاال البحةةة
يدددد ادددد دحا دددد احتعالدددد شلعودددد بلححدحا دددد احتددددلب .تحددددل تددددل اح ليددددل احل حضلا
هردددلة وشلدددل ةا للحددد أ لدددل اددد و دددى احلدددضل ى احت ايددد احدددت اح ليدددل احل حضلايددد اددد
. بلءددددن احش حدددد احضل ددددل حر ددددى ليددددل حتعالدددد شلعودددد بلححدحا دددد احتددددلب دحا دددد ا
% 86.5لددددددد دددددددح عل ددددددد ل 1.7538احر ح اا ددددددد حدددددددت اح ليدددددددل احل حضلايددددددد
% 97.5% ات حدددددد ر دددددداا لددددددل 64% ات حدددددد ر دددددداا يدلب دددددد 91.6ا لا دددددد
ددددح 80.70.بلءددددن احش حدددد احضل ددددل حر ددددى احلددددضل ى احت ايدددد احددددت اح ليددددل احل حضلايدددد
% ت حدددددد 28.6% ت حدددددد ر دددددداا يدلب دددددد 95.1% لا دددددد 81.1 عل دددددد للدددددد
..%64.6 ر اا لل
ليددددل احر ح اا دددد احددددت اح ليددددل احل حضلايدددد ااحلددددضل ى يحكددددص لددددح تال و ددددى الإسةةةةتنتا
احت ايدددد احددددت اح ليددددل احل حضلايدددد ادددد احالدددد الأان ددددص احتحدددد تح ادددد اء حلحطدددد ص
.ح ك لأع ضلد ء احتل ح احتح اح
اححطدددد ص احح كدددد ححشددددت لء –احلددددضل ى احت ايدددد –اح ليددددل حلحضلابدددد الكلمةةةةاط الدالةةةةة
. الع دلد